Management of chronic obstructive pulmonary disease: the Swiss guidelines. Official Guidelines of the Swiss Respiratory Society.
Explore the source record for details and available documents.
Chronic Disease↗
Biomedical subjects
M Gugger
Publications and source records attributed to M Gugger.
[Virtual endoscopy of the upper, central and peripheral airways with multirow detector CT].
Virtual endoscopy of the upper, central and peripheral airways (virtual laryngoscopy or virtual bronchoscopy) produces endoluminal images similar to those of fiberoptic endoscopy. In particular, virtual endoscopy is useful for the assessment of endoluminal tumor extent and tracheobronchial stenosis. Especially since the introduction of multirow detector CT, high-resolution virtual-endoscopic images of the airways can be reconstructed. Either surface rendering or volume rendering can be used for realistic depiction of the airways. Semitransparent color-coded volume rendering is advantageous, because adjacent structures can be displayed in addition to endoluminal views. A major advantage of virtual endoscopy over fiberoptic endoscopy is its non-invasiveness. With virtual endoscopy, even a high-grade stenosis is passable, enabling evaluation of the distal airways. Disadvantages are its inability to depict mucosal color and to perform therapeutic maneuvers. In comparison to other CT display modes, virtual endoscopy allows a more realistic assessment of tracheobronchial stenosis than axial CT slices and multiplanar reformats. Virtual endoscopy of the airways can be used complementary to fiberoptic endoscopy before tracheotomy, stent implantation or lung resection and for post-operative follow-up. In the future, virtual airway endoscopy will be increasingly applied for interactive virtual reality guidance of airway procedures such as bronchoscopy and surgery.
Bronchial Diseases↗
Y(1)-mediated effect of neuropeptide Y in cancer: breast carcinomas as targets.
Overexpression of selected peptide receptors in human tumors has been shown to represent clinically relevant targets for cancer diagnosis and therapy. Neuropeptide Y (NPY) is a peptide neurotransmitter mediating feeding behavior and vasoconstriction. It has never been shown to be involved in human cancer. We show here, using in vitro receptor autoradiography, a NPY receptor incidence of 85% in primary human breast carcinomas (n = 95) and of 100% in lymph node metastases of receptor-positive primaries (n = 27), predominantly as Y(1) subtype, whereas non-neoplastic human breast expressed Y(2) preferentially. Y(1) mRNA was detected in Y(1)-expressing tumors by in situ hybridization, whereas Y(2) mRNA was found in normal breast tissue. The strong predominance of Y(1) in breast carcinomas compared with Y(2) in normal breast suggests that neoplastic transformation can switch the NPY receptor expression from Y(2) to Y(1) subtype. Moreover, in Y(1)-expressing human SK-N-MC tumor cells, an NPY-induced, dose-dependent inhibition of tumor cell growth of >40% was observed, suggesting a functional role of NPY in cancer, mediated by Y(1). NPY should therefore be added to the list of small regulatory peptides related to cancer. The high incidence of Y(1) in in situ, invasive, and metastatic breast cancers allows for the possibility to target them for diagnosis and therapy with NPY analogues.
Adult↗
The bmi-1 oncoprotein is differentially expressed in non-small cell lung cancer and correlates with INK4A-ARF locus expression.
Genes of the polycomb group function by silencing homeotic selector genes that regulate embryogenesis. In mice, downregulation of one of the polycomb genes, bmi-1, leads to neurological alterations and severe proliferative defects in lymphoid cells, whilst bmi-1 overexpression, together with upregulation of myc-1, induces lymphoma. An oncogenic function has been further supported in primary fibroblast studies where bmi-1 overexpression induces immortalization due to repression of p16/p19ARF, and where together with H-ras, it readily transforms MEFs. It was the aim of this study to assess the expression of bmi-1 in resectable non-small cell lung cancer (NSCLC) in association with p16 and p14ARF (=human p19ARF). Tumours (48 resectable NSCLC (32 squamous, 9 adeno-, 2 large cell, 4 undifferentiated carcinomas and 1 carcinoid); stage I, 29, II, 7, III, 12; T1, 18, T2, 30; differentiation: G1 12, G2 19, G3 17) were studied by immunohistochemistry for protein expression and by comparative multiplex PCR for gene amplification analysis. In tumour-free, normal lung tissue from patients, weak - moderate bmi-1 staining was seen in some epithelial cells, lymphocytes, glandular cells and in fibroblasts, whereas blood, endothelial, chondrocytes, muscle cells and adipocytes did not exhibit any bmi-1 expression. In tumours, malignant cells were negative/weakly, moderately and strongly positive in 20, 22 and 6 cases, respectively. As assessed by multiplex PCR, bmi-1 gene amplification was not the reason for high-level bmi-1 expression. Tumours with moderate or strong bmi-1 expression were more likely to have low levels of p16 and p14ARF (P = 0.02). Similarly, tumours negative for both, p16 and p14ARF, exhibit moderate-strong bmi-1 staining. 58% of resectable NSCLC exhibit moderate-high levels of bmi-1 protein. The inverse correlation of bmi-1 and the INK4 locus proteins expression (p16/p14ARF) supports a possible role for bmi-1 misregulation in lung carcinogenesis.
Aged↗
Effects of linear polyethylenimine and polyethylenimine/DNA on lung function after airway instillation to rat lungs.
Lung transplantation is an acceptable treatment option for various end-stage pulmonary diseases, but long-term survival currently lags behind that after transplantation of other solid organs. We hypothesized that gene transfer to grafts before transplantation may be a useful method to deliver antioxidant and/or anti-inflammatory genes to modulate these processes. For this purpose, we assessed the efficiency of gene transfer and effects on lung function of the synthetic polycation, linear polyethylenimine (PEI), after airway instillation to the lungs of Fischer rats. Twenty-four hours after gene delivery, reporter gene activity in DNA/PEI treated rats was approximately 12-fold higher than that in rats treated with naked DNA, but by 72 hours there was no significant difference between groups and activity had decreased by at least 85%. Function of the transfected left lung was assessed by measuring arterial PaO(2) levels and was found to be significantly lower at 24 and 72 hours after gene transfer in the PEI/DNA group compared with the naked DNA group. The deterioration in lung function correlated with histological findings. Rats treated with PEI alone and sacrificed after 72 hours showed an impairment in lung function similar to that seen with PEI/DNA treatment. Our studies highlight the importance of assessing the functional capacity of a graft after gene transfer to determine suitability for subsequent transplantation.
Animals↗
Lobar pulmonary interstitial emphysema in a premature infant on continuous positive airway pressure using nasal prongs.
Unilobar pulmonary interstitial emphysema may emerge in extremely low birth weight infants without mechanical ventilation but on continuous positive airway pressure using nasal prongs.
Female↗
Pulmonary function testing after operative stabilisation of the chest wall for flail chest.
OBJECTIVE: This is a prospective evaluation of chest wall integrity and pulmonary function in patients with operative stabilisation for flail chest injuries. METHODS: From 1990 to 1999, 66 patients (56 men, 10 women; mean age 52.6 years) with antero-lateral flail chest (> or =4 ribs fractured at > or =2 sites) underwent surgical stabilisation using reconstruction plates. Clinical assessment and pulmonary function testing were performed at 6 months following surgery. RESULTS: Fifty-five (83%) patients had various combinations of injuries of the thorax, head, abdomen and extremities. Sixty-three (95.5%) patients underwent unilateral and 3 (4.5%) patients bilateral stabilisation with a median delay of 2.8 days (range 0-21 days) from admission. The 30-day mortality was 11% (seven of 66 patients). Immediate postoperative extubation was feasible in 31 of 66 patients (47%) and extubation within 7 days following stabilisation in 56 of 66 patients (85%). No plate dislocation was observed during the follow-up. The shoulder girdle function was intact in 51 of 57 patients (90%). Chest wall complaints were noted in 6 of 57 (11%) patients, requiring removal of implants in three cases. All patients returned to work within a mean period of 8 (range 3-16) weeks following discharge. Pulmonary function testing (n=50) at 6 months after the operation revealed a significant difference of predicted vs. recorded vital capacity (VC) and forced expiratory volume in 1s (FEV1) (P=0.04 and P=0.0001, respectively; Wilcoxon signed-rank test). The median ratio of the recorded and predicted total lung capacity (TLC) was shown to be significantly higher than 0.85 (P=0.0002; Wilcoxon signed-rank test), indicating prevention of pulmonary restriction. CONCLUSION: Antero-lateral flail chest injuries accompanied by respiratory insufficiency can be effectively stabilised using reconstruction plates. Early restoration of the chest wall integrity and respiratory pump function may be cost effective through the prevention of prolonged mechanical ventilation and restriction-related working incapacity.
Adult↗
Outcome after unilateral lung volume reduction surgery in patients with severe emphysema.
OBJECTIVE: Bilateral lung volume reduction surgery (LVRS) has emerged as a palliative treatment option in patients with severe pulmonary emphysema. However, it is not known if a sustained functional improvement can be obtained using an unilateral approach. METHODS: We hypothesized that a palliative effect can also be obtained by unilateral LVRS and prospectively assessed lung function, walking distance, and dyspnea before and 3, 6, 12, 18, 24 and 36 months after unilateral LVRS. RESULTS: Twenty-eight patients were operated by the use of video-assisted thoracoscopic surgery (VATS) with a mean follow-up of 16.5 months (range 3-36 months). Forced expiratory volume in 1 s (FEV1) was significantly improved up to 3 months (1007+/-432 compared to 1184+/-499 ml, P<0.001), residual volume up to 24 months (4154+/-1126 compared to 3390+/-914 ml, P<0.01), dyspnea up to 12 months (modified Borg dyspnea scale 6.6+/-1.8 compared to 3.9+/-1.8, P=0.01) and walking distance up to 24 months (343+/-107 compared to 467+/-77 m, P<0.05) after unilateral LVRS compared to preoperative values. Overall, 25 of 28 patients reported a subjective benefit after unilateral LVRS. There was no 30-day mortality. Only two patients required surgery on the contralateral side after 4.5 and 6 months, respectively, both suffering from alpha-1-antitrypsin deficiency. CONCLUSIONS: Unilateral LVRS by the use of VATS results in a sustained beneficial effect, improving walking distance and dyspnea for up to 24 months in patients with severe emphysema. The preservation of the contralateral side for future intervention if required renders unilateral LVRS an attractive concept in this difficult palliative situation.
Aged↗
Molecular characterization of planktic cyanobacteria of Anabaena, Aphanizomenon, Microcystis and Planktothrix genera.
Toxic and non-toxic cyanobacterial strains from Anabaena, Aphanizomenon, Calothrix, Cylindrospermum, Nostoc, Microcystis, Planktothrix (Oscillatoria agardhii), Oscillatoria and Synechococcus genera were examined by RFLP of PCR-amplified 16S rRNA genes and 16S rRNA gene sequencing. With both methods, high 16S rRNA gene similarity was found among planktic, anatoxin-a-producing Anabaena and non-toxic Aphanizomenon, microcystin-producing and non-toxic Microcystis, and microcystin-producing and non-toxic Planktothrix strains of different geographical origins. The respective sequence similarities were 99.9-100%, 94.2-99.9% and 99.3-100%. Thus the morphological characteristics (e.g. Anabaena and Aphanizomenon), the physiological (toxicity) characteristics or the geographical origins did not reflect the level of 16S rRNA gene relatedness of the closely related strains studied. In addition, cyanobacterial strains were fingerprinted with repetitive extragenic palindromic (REP)- and enterobacterial repetitive intergenic consensus (ERIC)-PCR. All the strains except two identical pairs of Microcystis strains had different band profiles. The overall grouping of the trees from the 16S rRNA gene and the REP- and ERIC-PCR analyses was similar. Based on the 16S rRNA gene sequence analysis, four major clades were formed. (i) The clade containing filamentous heterocystous cyanobacteria was divided into three discrete groups of Anabaena/Aphanizomenon, Anabaena/Cylindrospermum/ Nodularia/Nostoc and Calothrix strains. The three other clades contained (ii) filamentous non-heterocystous Planktothrix, (iii) unicellular non-heterocystous Microcystis and (iv) Synechococcus strains.
Anabaena↗
Restless legs syndrome: a clinical study of 55 patients.
BACKGROUND: Restless legs syndrome (RLS) is a common sleep disorder. In 1995, clinical criteria for the diagnosis of RLS were defined. OBJECTIVE: To describe the clinical spectrum in a series of unselected RLS patients meeting the new diagnostic criteria. METHODS: We prospectively assessed by questionnaire and clinical assessment the characteristics of 55 consecutive RLS patients (35 women, 20 men; mean age = 62 +/- 16 years). RESULTS: In 27% of the patients, RLS started before the age of 20 years (early-onset RLS). Sensory disturbances were painful in 56% of patients and felt in legs (98%), arms (35%), and 'internally' (45%). Motor disturbances included 'dyskinesias while awake' (36%). Insomnia (58%) was commoner than hypersomnia (24%). In 67% of the patients, no etiology of RLS was found (idiopathic RLS). Early-onset RLS was more commonly familial (p = 0.01) and associated with 'growing pains' (p = 0.005) than late-onset RLS. Patients with RLS and hypersomnia were younger (p = 0.01) and less commonly had painful sensations (p = 0.04) than patients with RLS and insomnia. Patients with idiopathic RLS were younger (p = 0.004), and less commonly had insomnia (p = 0.01) than patients with symptomatic RLS. CONCLUSIONS: RLS is a clinically pleomorphic syndrome, reflecting the contribution of multiple genetic and acquired factors in the pathogenesis of RLS.
Adult↗
[Prevalence of sleep disorders in an employed Swiss population: results of a questionnaire survey].
BACKGROUND: The aim of the study was to demonstrate the variety of sleep disorders occurring in a working population in Switzerland and to estimate the prevalence of the main sleep disorders in this Swiss cohort. We also intended to demonstrate that with just a few systematic questions a straightforward diagnostic workup is possible in general practice. METHODS: A questionnaire was sent to all 1473 clerks of the Berne main post office. The questions allowed a choice between "yes" or "no", or often (= +3), occasionally (= +2), rarely (= +) and never (= 0). Daytime sleepiness was assessed by the Epworth Sleepiness Scale. RESULTS: 668 questionnaires (45%) were available for analysis. Daytime sleepiness, assessed by an Epworth score > or = 10, was found in 13% of the respondents. Short sleep (< 7 h sleep) was reported in 47%, and long sleep (> 9 h sleep) in 5% of this population. Specific questions clearly suggested obstructive sleep apnoea in 6%, restless-legs syndrome in 4%, disorders of initiating and maintaining sleep in 19% and narcolepsy in 0.5% of respondents. CONCLUSION: Chronic sleep insufficiency and sleep complaints appear to be frequent in this relatively young Swiss working population. The questionnaire-based estimated prevalence of the main sleep disorders is comparable to previously published international data.
Adult↗
Sleepiness-related accidents in sleep apnea patients.
The frequency of motor vehicle and working accidents was analyzed by means of a strictly anonymous questionnaire in 156 patients with sleep apnea syndrome (SAS) and in 160 age-gender matched controls. In the SAS group 12.4% of all drivers had motor vehicle accidents as compared to 2.9% in the control group (p<0.005). The motor vehicle accident rate was 13.0 per million km in patients with more severe SAS (AHI > 34/h, n=78) as compared to 1.1 in patients with milder SAS (AHI 10-34/h, n=78) (p<0.05), and 0.78 in control group (p<0.005), respectively. The accident rates in both patients and the control group were also greater than the rate of 0.02 "accidents due to sleepiness" per one million km in the Swiss driving population as reported by official statistics. During treatment with nasal continuous airway pressure (nCPAP) in 85 SAS patients, the motor vehicle accident rate dropped from 10.6 to 2.7 per million km (p<0.05). We conclude that patients with moderate to severe SAS have an up to fifteen-fold risk increase of motor vehicle accidents that constitutes a serious and often underestimated hazard on the roads, which can be reduced by adequate treatment.
Accidents, Traffic↗
Prognostic relevance of Masaoka and Müller-Hermelink classification in patients with thymic tumors.
BACKGROUND: To compare the prognostic relevance of Masaoka and Müller-Hermelink classifications. METHODS: We treated 71 patients with thymic tumors at our institution between 1980 and 1997. Complete follow-up was achieved in 69 patients (97%) with a mean follow up-time of 8.3 years (range, 9 months to 17 years). RESULTS: Masaoka stage I was found in 31 patients (44.9%), stage II in 17 (24.6%), stage III in 19 (27.6%), and stage IV in 2 (2.9%). The 10-year overall survival rate was 83.5% for stage I, 100% for stage IIa, 58% for stage IIb, 44% for stage III, and 0% for stage IV. The disease-free survival rates were 100%, 70%, 40%, 38%, and 0%, respectively. Histologic classification according to Müller-Hermelink found medullary tumors in 7 patients (10.1%), mixed in 18 (26.1%), organoid in 14 (20.3%), cortical in 11 (15.9%), well-differentiated thymic carcinoma in 14 (20.3%), and endocrine carcinoma in 5 (7.3%), with 10-year overall survival rates of 100%, 75%, 92%, 87.5%, 30%, and 0%, respectively, and 10-year disease-free survival rates of 100%, 100%, 77%, 75%, 37%, and 0%, respectively. Medullary, mixed, and well-differentiated organoid tumors were correlated with stage I and II, and well-differentiated thymic carcinoma and endocrine carcinoma with stage III and IV (p < 0.001). Multivariate analysis showed age, gender, myasthenia gravis, and postoperative adjuvant therapy not to be significant predictors of overall and disease-free survival after complete resection, whereas the Müller-Hermelink and Masaoka classifications were independent significant predictors for overall (p < 0.05) and disease-free survival (p < 0.004; p < 0.0001). CONCLUSIONS: The consideration of staging and histology in thymic tumors has the potential to improve recurrence prediction and patient selection for combined treatment modalities.
Adult↗
Functional assessment of chest wall integrity after methylmethacrylate reconstruction.
BACKGROUND: All patients with extensive resection of the anterolateral chest wall and the sternum followed by reconstruction with methylmethacrylate substitutes were assessed prospectively 6 months after the operation to delineate chest wall integrity with pulmonary function and cine-magnetic resonance imaging. METHODS: Twenty-six patients underwent chest wall reconstruction by use of methylmethacrylate between 1994 and 1998 due to primary tumors in 35%, metastases in 27%, T3 lung cancer in 19%, and debridement for radionecrosis and osteomyelitis in 19% of patients. Three to eight ribs were resected and additional sternum resection was performed in 39% of patients. RESULTS: There was no 30-day mortality. All patients were extubated after the operation without need for reintubation. Prosthesis dislocation occurred in 1 patient and infection in 2 patients during follow-up. Nineteen patients (73%) suffered no restrictions of daily activities. Clinical examination revealed normal shoulder girdle function in 77% of patients. There was no significant difference between preoperative and postoperative FEV1 (forced expiratory volume in 1 second) measurements in patients with lobectomy or wedge resections. Cinemagnetic resonance imaging revealed concordant chest wall movements during respiration in 92% of patients without paradoxical movements or implant dislocations being observed. CONCLUSIONS: Large defects of the anterolateral chest wall and sternum can be reconstructed efficiently with methylmethacrylate substitutes with minimal morbidity and excellent cosmetic and functional outcome.
Adult↗
[Hypersomnia--etiology, clinic, diagnosis and therapy of excessive sleepiness].
Hypersomnia (excessive sleepiness) refers to an increased sleep propensity with a subjective craving for sleep, involuntary naps and "sleep attacks" during the day and/or prolonged nighttime sleep with sleep drunkeness. Excessive sleepiness should be separated from fatigue and lack of energy associated with a variety of medical and psychiatric diseases. Hypersomnia is reported by 2-5% of the adult population and can lead to poor work, accidents and neuropsychiatric disturbances. Sleep apnea syndrome (SAS), narcolepsy, chronic sleep deprivation (insufficiency), and restless legs/periodic limb movements in sleep syndrome (RLS/PLMS) represent the most common causes of hypersomnia. The diagnosis of these conditions can often be suspected on clinical grounds. However, an overnight polysomnography and a multiple sleep latency test are often additionally required for definite diagnosis. Treatment options include nasal CPAP for SAS, stimulants for narcolepsy, sleep prolongation for sleep insufficiency, and dopaminergic agents for RLS/PLMS.
Adult↗
[Effectiveness of nasal CPAP-treatment (continuous positive airway pressure)].
Nasal continuous positive airway pressure (n-CPAP) is an effective treatment for the obstructive sleep apnea syndrome (OSAS). It is currently regarded as the first line therapy for OSAS. The principal indication for n-CPAP treatment is daytime sleepiness. Nasal-CPAP improves daytime sleepiness dramatically in severe cases and the effect is objectively measurable with the multiple sleep latency test (MSLT). It is noteworthy that n-CPAP also improves symptoms, subjective daytime sleepiness, cognitive function, IQ, mood, quality of life and driving ability already in patients with mild sleep apnea with an apnea/hypopneaindex (AHI) between 5 and 15 per hour of sleep during overnight polysomnography. Although not yet 100% robust, there is clear evidence that patients with OSAS have an increased frequency of systemic hypertension. Some early and imperfect studies suggest that CPAP reduces cardiovascular and cerebrovascular outcomes; however unequivocal evidence that n-CPAP reduces mortality is still awaited. There is now good evidence that treatment with n-CPAP reduces the two- to sevenfold increased risk of road accidents of untreated patients with OSAS. In summary, there exists abundant evidence today that n-CPAP is an efficient therapy for symptomatic patients with the obstructive sleep apnea syndrome. A trial with n-CPAP is therefore justified in all symptomatic patients. Based on the large number of randomized controlled trials of n-CPAP a therapeutic trial is indicated even in only mildly symptomatic patients with OSAS. Nasal-CPAP use and outcomes of therapy can be improved by provision of an intensive CPAP-education and support program.
Accidents, Traffic↗
[Nocturnal measurements of intraocular pressure in patients with normal-tension glaucoma and sleep apnea syndrome].
BACKGROUND: About half of all normal-tension glaucoma patients and about one third of all primary open-angle glaucoma patients have sleep apnea syndrome. If sleep apnea syndrome causes some cases of glaucoma, the optic nerve damage could result from repetitive nocturnal hypoxias or from repetitive intraocular pressure elevations at the end of the apneas. In this study, we determined the intraocular pressure at the end of long apneas. PATIENTS AND METHODS: In three patients having sleep apnea syndrome and normal-tension glaucoma we recorded in a sleep laboratory during at least six hours of sleep the respiration (oxymetry, nasal and oral air flow, and inductive plethysmography). The intraocular pressure was measured with a pneumatonometer at predetermined times and compared to the values measured at the end of prolonged apneas. RESULTS: The intraocular pressure during normal respiration was in the first patient 19.5 +/- 1.0 mm Hg OD and 19.3 +/- 1.7 mm Hg OS, in the second patient 25.0 +/- 4.2 respectively 25.5 +/- 4.9 mm Hg and in the third one 22 +/- 1.0 respectively 21.3 +/- 1.3 mm Hg. At the end of prolonged apneas the intraocular pressure was in the first patient 19.0 +/- 0.0 mm Hg OD and 19.5 +/- 0.7 mm Hg OS, in the second patient 26.5 +/- 0.6 and 26.8 +/- 0.1 mm Hg and in the third one 20.0 +/- 0.0 respectively 21.0 +/- 0.0 mm Hg. The difference between intraocular pressures during normal respiration and at the end of prolonged apneas was not significant (p > 0.1 for each comparison, paired t-test). CONCLUSIONS: We did not find an increase of intraocular pressure at the end of prolonged apneas compared to periods of normal respiration in patients with sleep apnea syndrome and normal-tension glaucoma. If sleep apnea syndrome causes some cases of glaucoma, it seems more probable that the the optic nerve is damaged by the repetitive hypoxias. Alternatively, an unknown factor might induce both, sleep apnea syndrome and normal-tension glaucoma.
Aged↗
[Safety profile of zolpidem: two studies of 3805 patients by Swiss practitioners].
Evaluation and treatment of insomnia are frequent procedures in the physician's everyday practice, since many patients seek medical treatment for this condition. Knowledge of pharmacological therapeutical alternatives is therefore decisive, in order to identify the most efficaceous and safe therapy for the patient among the available hypnotics. The short-acting hypnotic zolpidem has been investigated in Switzerland in two multicenter safety studies in ambulatory practice. In the first study 8.9% (n = 125 of 1,972 treated patients), and in the second 7.2% of the patients (n = 175 of 1,833 treated patients) reported an adverse event. The most frequent events were related to the central nervous system (CNS) (somnolence, headache, confusion, vertigo); gastrointestinal and cutaneous symptoms were the most frequent non CNS-dependent effects. New, unknown or serious adverse events were not found and no specific risk factor or population at risk was identified. The safety profile of zolpidem is consistent with its known pharmacological properties, the results of previous clinical trials and the international experience obtained in large patients groups.
Adolescent↗